VA report: DDx for elevated LDH

Today in report Stefan presented a great case involving alcohol withdrawal, cholestatic and hepatocellular liver injury, thrombocytopenia and pancreatitis. The unifying dx is likely ETOH, but a good discussion ensued regarding LDH, and if very elevated LDH can refine your ddx.

What is LDH? Lactate dehydrogenase is an enzyme found in nearly all animal cells. It converts pyruvate to lactic acid. Since LDH is expressed in most tissues, it can be a marker for tissue damage.

What causes LDH elevation? (A HUGE LIST!)

The take home here is that LDH is non-specific for many conditions. The list is below, but honestly it’s more important to remember that LDH can be elevated when any form of tissue death occurs.

The degree of LDH elevation can sometimes narrow the differential and the test characteristics have been studied.

In a paper entitled “Diagnostic and prognostic value of very high serum lactate dehydrogenase in admitted medical patients”, very high LDH (>800) occurs more commonly in hematologic malignancy, liver mets, and infections (don’t forget about PCP PNA in our patients!).

Causes of an elevated serum lactate dehydrogenase level
Cardiac Myocyte injury

  • Demand ischemia
  • Trauma, cardiovascular surgery
  • Toxins
  • Infection (myocarditis, rheumatic fever)
  • Drugs (alcohol, chemotherapy, cocaine, methysergide, carbon monoxide)

 

Hepatic congestion

  • Heart failure

 

Hemolysis

  • Prosthetic valves
Central nervous system disorders
  • Bacterial meningitis
  • Cerebral hemorrhage
  • Cerebral venous thrombosis
Drug-induced
  • Neuroleptic agents (neuroleptic malignant syndrome)
  • Withdrawal of L-Dopa or dopamine agonist
  • Serotonin syndrome
  • Malignant hyperthermia
  • Recreational drugs
  • Myopathies (colchicine, antimalarials, cholesterol-lowering drugs, cocaine, alcohol, glucocorticoid)
Endocrine
  • Hypothyroidism
  • Acromegaly
  • Cushing’s syndrome
  • Diabetic muscle infarction
Gastrointestinal
  • Acute pancreatitis
  • Intestinal obstruction
  • Early acute hepatitis
  • Ischemic hepatitis
Hematologic Hemolytic anemias

  • Inherited (spherocytosis, sickle cell disease, deficiency of red blood cell enzymes)
  • Acquired (microangiopathic hemolytic anemia, PNH, immune hemolysis)

 

Ineffective erythropoiesis

  • Pernicious anemia, folic acid deficiency
  • Iron deficiency
  • Primary myelofibrosis
Infection
  • Pneumocystis pneumonia (late)
  • Tuberculosis
  • Malaria
  • Parasitic
  • Legionnaires disease
  • Histoplasmosis
  • Toxoplasmosis
Malignancy
  • Leukemias
  • Lymphomas
  • Solid tumors (testicular germ cell tumors)
  • Tumor lysis syndrome (large tumor burden)
Neuromuscular
  • Myopathies (inherited, acquired, drug)
  • Periodic paralyses
Pregnancy
  • Preeclampsia
  • Adnexal mass in pregnancy
  • HELLP syndrome
Pulmonary
  • Pulmonary embolism, infarction
  • Pulmonary alveolar proteinosis
Renal
  • Renal infarction
Rheumatologic
  • Dermatomyositis
  • MCTD
  • Rheumatoid arthritis
  • Scleroderma
  • Sjögren’s syndrome
  • SLE
Trauma
  • Rhabdomyolysis
  • Surgery
Vasculitis
  • Polyarteritis nodosa
  • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss vasculitis)
  • Granulomatosis with polyangiitis [Wegener’s]
  • Behçet’s syndrome
  • Sarcoidosis
Idiosyncratic LDH elevation The presence of macro-LDH (LDH combined with an immunoglobulin), not associated with any symptoms or particular disease

PMID: 25167691

 

 

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